C2H2 Zinc-Finger Transcription Factors Coordinate Hormone–Stress Crosstalk to Shape Expression Bias of the Flavonoid Pathway in Safflower (<em>Carthamus tinctorius</em> L.)

C2H2-type zinc-finger proteins (ZFPs) are key transcriptional regulators of plant stress biology, yet their diversity and function in safflower remain unclear. Leveraging the “Jihong-1” reference, we investigated the C2H2 repertoire in safflower and identified 62 CtC2H2 genes. Comparative phylogeny with Arabidopsis resolved six robust subfamilies that share diagnostic exon-intron organizations and the conserved QALGGH motif. Promoter surveys uncovered abundant light-responsive elements (G-box, Box 4, GT1-motif) together with hormone-responsive ABRE and CGTCA/TGACG motifs, indicating multilayered regulation. Consistent with these features, RNA-seq and qRT-PCR revealed tissue-specific expression and strong inducibility under four treatments (cold, abscisic acid (ABA), methyl jasmonate (MeJA), and UV-B, with ABA eliciting the most pronounced responses, many genes peaking at 24 h. Functionally, ABA treatment doubled total leaf flavonoids at 24 h and shifted the flavonoid pathway transcriptome: CtCHS, CtFLS, CtDFR and CtANS increased, while CtF3H and CtF3′H decreased, aligning with induction of several CtC2H2 members (e.g., CtC2H2-02/15/21/22/23/24/35/45/47). All CtC2H2 proteins are predicted nuclear, hydrophilic factors with diverse pI values, supporting a role in transcriptional control. Together, these results establish a curated catalogue of safflower C2H2 ZFPs, define their stress- and hormone-responsive expression modules, and nominate candidate regulators linking ABA signaling to flavonoid biosynthesis. This resource provides tractable targets for engineering stress resilience and metabolite accumulation in a medicinal and oilseed crop.